That's an interesting question, Avatargirl . . . I think it could be answered a couple different ways...
First of all, the original 1960's anime was VERY popular in the US (the world's largest single market at the time). I believe that if NBC hadn't cancelled the series, AND Tezuka Productions had changed over to color from black and white, the series would have CONTINUED to grow in popularity (NBC were concerned it was too much work to rewrite scripts, etc. because of issues of complexity and "violence" - and that meant too expensive). So I think the original COULD have been wildly successful.
Next, if Astro had been a female character, I think she would still have had to face the same issues as the male Astro Boy (black and white, violence, and lack of financial commitment from NBC) - so I don't think gender would have mattered much there.
BUT - maybe in the 80's version . . . where the format was full color, and a higher quality animation . . . if Astro had been cast as a female lead character, it COULD have been more successful (and, after all, that WAS Dr. Tezuka's original idea). Look how popular Uran is - imagine the dolls and other merchandise Tezuka could have profited from. The idea of a girl hero is good, but it might lose some male fans (unless she were cast as a teenaged girl, and very attractive - then she'd be more like female manga/anime lead characters we see today, I guess).
Interesting to think about. I was drawn to the series because of the storyline, but it didn't really matter if "Astro" were a boy or a girl. In fact I wrote to "Channel 5" back in 1964 to suggest "they" include an Astro Girl as Astro's sister (I included a drawing too). You can imagine my shock when Uran turned up several months later (with the name "Astro Girl") - the most amazing part is that I had put a dark colored skirt and white top on my drawing, which is how Uran was originally dressed. I had included boots like Astro and was disappointed to see they were missing! I actually believed my letter had something to do with her being part of the show (quite a thrill for a 10 year old girl). Of course it was just coincidence!
