"I didn't think about it at all because the book had come out and been so successful," said Lowe at the annual Television Critics Association (TCA) panel Wednesday in Beverly Hills.
O'Reilly's "Killing Kennedy," which came out last year and was a bestseller, examined the events leading up to President John F. Kennedy's death.
Lowe plays Kennedy in the film, and says like O'Reilly's book, National Geographic Channel's version will also present a unique perspective on the country's 35th president.
"The way this story is told I've never seen before," he said.
Yes, it features Lowe as the doomed president and Ginnifer Goodwin as first lady Jackie Kennedy, but it also depicts Lee Harvey Oswald's life before killing Kennedy.
Will Rothhaar, who takes on the role of one of the most notorious killers in American history, says he tried to make Oswald relatable.
"You will look at him and say, 'I've been there or I've felt that,'" he said.
Michelle Trachtenberg plays Oswald's wife, Marina. She said about 80 per cent of her dialogue in the movie is in Russian and she learned that, like many people at that time, she was a big fan of President Kennedy.
Goodwin was not physically present at the press event but instead live via satellite from Vancouver, Canada where she films the ABC series "Once Upon a Time."
She said one of the most challenging parts of the role was Jackie Kennedy's famous aristocratic, breathy voice. Ultimately, the actress decided to not mimic her too much because it sounded like an impression.
"A dialect coach said the more I nailed it the less she believed me. (The voice) is so unrelatable today."
Lowe, too, had the challenge of recreating Kennedy's look and speech, which the self-professed history nut says he believes presidents today are even influenced by. He said he "could imitate every single president doing their version of JFK."
The actor likes the challenge of portraying historical figures. He hopes to play President Ulysses S. Grant in a role that he calls "a dream project."
This is not National Geographic's first foray into turning an O'Reilly book into a made-for-TV movie. It also adapted O'Reilly's "Killing Lincoln" to record ratings for the network.
"Killing Kennedy" will air in November on Nat Geo, coinciding with the 50th anniversary of Kennedy's death.
Alicia Rancilio covers Entertainment for The Associated Press. Follow her online at http://www.twitter.com/aliciar